analgesics

ANALGESICS
ANALGESICS
I. Opioid (narcotic) analgesics
1. Agonists of opioid receptors – morphine
hydrochloride, promedol, omnopon, fentanil,
codeinн;
2. Agonists – antagonists and partly agonists of
opioid receptors – pentasocin, buprenorphine.
II. Nonnarcotic analgesics and nonsteroid
antiinflammatory drugs
acetysalycylic acid, paracetamol, analgin, indometacin,
butadion, ibuprofen, pyroxicam, diclofenac-sodium,
ketorolac, ketoprofen.
III. Substances with mixed mechanism of
action (opioid and nonoioid components)
tramadole
NARCOTIC
ANALGESICS
The following structures take part in
perception of pain: thalamus, hypothalamus,
reticular formation, limbic system, occipital
and frontal areas of cortex
System which conducts and perceives pain -
nociceptive
System which contracts pain –
antinociceptive
Visceral pain
– from internal organs
Somatic pain
– bones, muscles, articulations, teeth,
ligaments, nerves
Opioid system
Contents:
• opioid receptors
• endogen opioid substances – endorphins,
encephalines, dinorphines
Subtypes of opioid receptors:
mu, delta, kappa, epsilon, sigma
Subtypes of opioid receptors
mu
Analgesia, depression of breathing, euphoria,
addiction
development,
sedative
effect,
depression of contents mocing through
digestive tract, miosis
kappa
Analgesia, sedative eefect, psychotomimetic
action
delta
Analgesia, euphoria, behaviour chnages
sigma
Mania, increasing of breathing frequency,
hallucinations, midriasis
Poppy
1. Papaver
rhoeas L.
2. Papaver
somniferum L.
1
2
Morphine hydrochloride
“mosaic action” on central nervous system
Effects of depression
•
•
•
•
analgesia
decreasing of frequency and depth of breathing
depressing of central links of coughing reflex
from the side of psychic sphere – somnolence, retardness
Effects of stimulation
•
•
•
•
vomiting (excitation of trigger zone of vomiting center)
bradycardia (increasing of tone of vagal nerve nuclei)
miosis (increasing of tone of n. oculomotorius nuclei)
euphoria (condition of full psychological wellness with
pleasant emotional feelings and feeling of physical comfort)
• increasing of activity of spinal cord intermediate neurons
ADMINISTRATION OF NARCOTIC
ANALGESICS
•
•
•
•
•
prophylaxis and treatment of pain shock
traumas
burns
acute myocardium infarction
premedication for potentiation of action of narcosis
drugs, analgesia in postoperative period
• colics
• to releive sufferings of oncologic patients of 4
clinical group (can’t be treated radically)
• acute abdomen (strong pain in abdominal cavity,
caused by perforation of ulcer, acute appendicitis,
acute intestinal impassability etc.) – only from the
moment then diagnosis becomes clear
MORPHINE HYDROCHLORIDE
Ways of introduction into organism
• subcutaneously and intramuscularly
(analgesic action after 10-15 min)
• after
oral introduction – presystemic
elimination
( 20-60 % enters general blood circulation)
• sublingually – quick absorption
• into epidural, subarachnoic spaces
• into brain ventricles
Duration of analgesic action – 4-6 hours
Maximal one-time dose of morphine is 0,02 g,
maximal day dose – 0,05 g
Side effects of morphine
• addiction
• tolerance
• vomiting (excitation of starting zone of
vomiting center)
• bradycardia (increasing of tone of n. vagus
nuclei)
• spasm of sphincters of gastro-intestinal tract
accompanied by constipations
• increasing of tone of smooth musculature of
urinary and bile-excreting tracts (retentions
of urination, bile stasis)
• Bronchial spasm
 pain that accompanies chronic diseases. In exceptional
CONTRAINDICATIONS FOR ADMINISTRATION OF
occasions it is introduced (not more than 1-2 injections) in
MORPHINE
case of pain which threatens
development of pain shock, for,
example, acute attach of ulcer disease
 children before the age of 2 years
 for aged from 2 to 6 years and elderly the drug should be
administered very carefully (breathing depression is possible)
 pregnancy and lactation
 anesthesia during child delivery (fetus breathing depression)
 skull traumas, brain hemorrhages (increasing of intracranial
pressure)
 depression of function of breathing center, damage of
respiratory organs, bronchial asthma
OMNOPON
 contains mixture if opium alkaloids
(48-50% morphine)
 does not cause spasms of smooth
musculature, as it contains alkaloids of
isochinoline raw
 is used for analgesia according to all the
indications of morphine hydrochloride, for
example, colics
Promedol
 duration of analgesic action - 3-4 hours
 moderate spasmolytic influence on smooth
musculature of internal organs
 stimulation of rhythmic contractions of
uterus
 does not depress breathing
 can be used for analgesia and stimulation
of child delivery
 in case of pain syndrome connected with
spasms of smooth musculature
Phentanil
 synthetic narcotic analgesic of short action
 analgesic activity is 300 times higher than of
morphine
 analgesic effect after intravenous introduction –
after 1-3min, lasts for 15-30min
 used with a narcoleptic droperidol (complex
drug – “talamonal”) for neuroleptanalgesia – a
variant of general anesthesia
Codeine
 opium alkaloid
 analgesic action is not strong, but
anticough effect is considerable
 administered as an anticough drug of
central action
 analgesic with weak activity combined with
non-narcotic analgesics (paracetamol) for
potentiation of the effect
Pentazotsin
 agonist-antagonist of opioid receptors
 it is a bit less dangerous in the aspect of addiction
development (in comparison with morphine)
 indicated in case of pain of medium intensity in
such conditions like other narcotic analgesics.
 it can cause increasing of blood pressure and
tachycardia that’s why it’s not advised to use in
case of acute myocardium infarction
 if it is administered for people with narcotic
addiction manifestations of abstinence develop
Buprenorphine
 Partly agonist of mu-opioid receptors
 Acts longer than morphine (approximately 6 hours)
 Analgesic activity is higher than of morphine, that’s
why it’s used in doses of 0,3-0,6 mg
 Indicated for pain decreasing in the same situations
as other narcotic analgesics
 May be used for detoxication and supporting
treatment of individuals who is addicted to heroine
TRAMADOL
 Analgesic activity is
not
weaker
than
activity of morphine
 In case of intravenous
administration
effect
develops after 5-10 min,
 if administered orally –
after 30-40 min, action
lasts for 3-5 hours.
ADMINISTRATION OF TRAMADOL
 surgery,
traumatology,
neurology, urology, oncology
gynecology,
 For all kinds of acute and chronic pain of
moderate
and
considerable
intensity,
including postoperative, traumatic pain!
 neuralgias
 diagnostic and therapeutic interventions
 oncologic pathology
Acute poisoning with narcotic analgesics
It is often observed in drug addicts death – from
breathing
depression






SYMPTOMS
dizziness
nausea, vomiting (rarely), heavy sweating
general weakness, somnolence, which after transfers into deep
dream and coma
pale and cyanotic skin, decreased body temperature
weak pulse, decreased blood pressure
rare and superficial breathing
Triad in case poisoning with morphine
 Acute miosis
 Pathological breathing of Chain-Stocks’ type
 Saved tendon reflexes
Treatments of acute poisoning
Naloxon
(antagonist of opium receptors)
i.v.- 0,4-1,2 mg
 stomach lavage (for morphine enterohepatic
circulation is typical) with 0,05-0,1% solution of
potassium permanganate and 0,5 % tannin solution
 salt laxative agents (sodium sulfate)
 forced diuresis
 atropine sulfate
 inhalation of carbogen (5-7 % СО2 and 93-95 % O2)
All narcotic analgesics cause
drug addiction – narcomania
Manifestations
psychological
dependence
physical dependence
tolerance
abstinence syndrome
NON-NARCOTIC
ANALGESICS
Types of action of non-narcotic
analgesics
•Analgesic
•Antipyretic
•Anti-inflammatory
(except paracetamol)
Mechanism of action of non-narcotic
analgesics activity
 depression of cyclooxygenases
 decreasing of prostaglandins synthesis in
peripheral tissues and in central nervous
system
 decreasing of sensitivity of nervous endings
and
depression
of
transduction
of
nociceptive impulses on the level of CNS
structures
 pain-relieving action of non-narcotic
analgesics is partly connected with their
anti-inflammatory activity
Indications for administration of
non-narcotic analgesics
headache
toothache
radiculitis
neuritis, neuralgias
myositits, myalgia
arthritis, arthralgia
pain,
connected
with
pelvic
organs
(dysmenorrhea)
for potentiation of their action – combinations
paracetamol with codein, analgin with dimedrol,
analgin with codein







Acetylsalicylic acid
Blocks
irreversably
cyclooxygenase
As a pyrolytic and analgesic drug –
0,25 and 0,5 g per time
As an antiinflammatory – 3-4 g per
day (for arthritis, myocarditis,
pleuritis, bronchitis etc.
For prophylaxis of thrombusformation (in case of ischemic
heart disease, thrombophlebitis
etc.) – daily dose – 80-100 mg
Analgin
(metamizol-sodium)
Baralgin (maxigan, spazgan,
spazmalgon, trigan)
analgin+pitophenon hydrochloride+pheniverinium bromide
• Ampoules
tablets
suppositories
• Analgesic and
spasmolytic
activity
Paracetamol
 analgesic and antipyretic drug
 maximal effect if the drug is introduced
orally – after 2 hours, lasts approximately
for 4 hours
 in case of durable administration of big
doses – damaging of liver and kidneys,
production of met-hemoglobin
Paracetamol
 Tablets
 Suppositories
 Syrups
 Soluble tablets
 Capsules
PARACETAMOL
Panadol (paracetamol)
Ketorolak (ketanov)
 according to analgesic activity it prevails over
effect of acetylsalicylic acid, indometacin and
equals to opioid analgesics
 moderate anti-inflammatory, antipyretic and
anti-aggregate effects
 high effectiveness in case of pain in
postoperative period, in oncology, during
child delivery, traumas, colics
 intramuscular introduction, orally
Analeptics
Analeptics are general CNS stimulants; they
stimulate vitally important centers
(respiratory and vasomotor) of the brain.
CLASSIFICATION OF ANALEPTICS UNDER
THE MECHANISM OF ACTION:
1. DIRECT-ACTING drugs, which stimulate centers of
the medulla oblongata:
Bemegride, Aethymizole, Caffeine
2. REFLECTORY-ACTING: cause reflectory timulation
of the respiratory center due to H-cholinoreceptors
of the sinus caroticus stimulation.
Cytitonum, Lobelinum
3. MIX-ACTION ANALEPTICS: They act as directly on
the respiratory and vaso-motor centres, as
reflectory on the chemoreceptors of vessels.
Cordiamine, Camphor, Sulfocaphocaine
CLASSIFICATION UNDER THE
INFLUENCE ON THE DIFFERENT
PARTS OF THE CNS:

Analeptics, act mainly on the cortex of the
brain: Caffeine

Analeptics, act mainly on the subcortex
centers: Bemegride, Aethymizole, Cytitonum,
Lobelinum, Cordiamine, Camphor,
Sulfocaphocaine

Analeptics, act mainly on the spinal cord:
Strychninum
INDICATIONS FOR USE OF
ANALEPTICS:
 Hypoxias, respiratory failure
 Overdosing or poisoning with narcotic drugs,
general anesthetics, alcohol, hypnotic drugs
 To speed up awakening action after narcosis
 Asphyxia of newborns;
 Shocks, collapses
 Prophylaxis of lung atelectasis and pneumonia
SIDE EFFECTS OF ANALEPTICS:
Nausea,
vomiting
Sezures
Increasing
of reflex excitation
Hyperventilation
Cardiac
arrythmia
PSYCHOMOTOR
STIMULANTS
PSYCHOMOTOR STIMULANTS
Derivatives of purine – caffeine
 Phenilalkilamines – phenamine
(amphetamine)
 Phenilalkilsydnonimins sydnocarb

Properties of psychomotor
stimulants
 Stimulate intellectual activity, speed
up thinking processes, temporarily
eliminate tiredness, somnolence
 Eliminate such manifestations of
neurosis as: subdepression, fatigue,
retardness
 Aren’t able to eliminate endogen
depression, which accompanies
psychic diseases
Caffeine
Mechanism of action
• Binding with adenosine (“purine”) receptors
in brain (endogen ligand of these receptors –
adenosine decreases processes of excitation
in CNS)
• Inhibiting of phosphodiesterase, which leads to
accumulation of cAMP and stimulation of many
physiological processes and metabolism
Usage of phychostimulating
influence of caffeine
 For stimulation of psychological
processes, workability, to eliminate
somnolence
 Enuresis, narcolepsy
 In case of poisoning with alcohol
 To speed up awakening after narcosis
Influence of caffeine on cardiacvascular system
Vessels
1. Stimulation of vasomotor center –
contraction of vessels, increasing of AP
2. Peripheral myotropic spasmolytic action
– dilation of vessels, decreasing of AP
Heart
1. Central action (increasing of n. vagus
tone) – bradycardia
2. Peripheral action (direct influence on
heart) – tachycardia, possible
extrasystolia
Influence of caffeine on cardiovascular system
 Contraction of brain vessels
 Dilation of kidney vessels, increasing of
diuresis
 Dilation of coronary vessels
In case of depression of centers of brain
stem (medulla oblongata) caffeine
shows stimulating properties, increases
blood pressure, stimulates breathing –
analeptic action
SIDE EFFECTS OF CAFFEINE
administered regularly – psychological
addiction – theism, which is accompanied by
development of abstinent syndrome
(retardness, fatigue, somnolence, depression)
 Tolerance
 Teratogenic action (inborn abnormalities)
 Increasing of frequency of stenocardia,
hypertension
 Acute attacks of ulcer disease (it increases
gastric secretion)
 Acute poisoning in case of overdosing
 If
NOOTROPIC DRUGS
(NEUROMETABOLIC
CEREBROPROTECTORS)
Neurometabolic
cerebroprotectors
 Derivatives of pyrrolidone –
 Derivatives of GABA –
 Neuropeptides –
pyracetam (nootropil)
aminalon, Na oxybutyrate
melatonin, sinacten-depot
 Cerebrovascular drugs –
sermion (nicergolin),
cavinton (vinpocetin), stugeron (cinnarisin),
pentoxyphylline (trental), xantynole
nicotinate
 Derivatives of piridoxine –
 Antioxidants –
 Others –
piritinol (encephabol)
mexidol, tocopherole acetate
cerebrolysine, actovegin, solkoseryl,
plant preparations
Properties of nootropic drugs
 Improvement of brain blood circulation,
promotion of collaterals development
 Psychostimulating effect, antiasthenic action
 Sedative, antidepressive action
 Antiepileptic, antiparkinsonic action
 Nootropic action
 Mnemotropic action
 Vasovegetative action
 Antihypoxic action
Administration of nootropic drugs
 Atherosclerosis of brain, vascular parkinsonism,
Alzheimer's disease
 Disorders of brain blood circulation in case of traumas
and intoxications, vascular diseases of brain
 Diseases of CNS, accompanied by decreasing of
intellect, memory
 Disorders of psychology (in elderly with schizophrenia,
depressions)
 To decrease manifestations of abstinence (alcoholism,
drug addiction)
 In neurology (neurasthenia, migraine, neuralgias,
radiculitis)
 In pediatrics in case if mental insufficiency
Piracetam (nootropil)
Cerebrolysin
Cinnarizin (stugeron)